Publications [#143104] of Thomas B Kepler

Papers Published

1. DA Culton, MW Nicholas, DO Bunch, QL Zhen, TB Kepler, MA Dooley, C Mohan, PH Nachman, SH Clarke, Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss., Journal of clinical immunology, United States, vol. 27 no. 1 (January, 2007), pp. 53-68, ISSN 0271-9142
   (last updated on 2008/01/31)

   Abstract:
   : We report here that dysregulation of CD19, a coreceptor that augments B-cell receptor (BCR) signaling, occurs at two B-cell differentiative stages in patients with systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic autoantibody (ANCA) associated small vessel vasculitis (SVV). The naïve B cells of nearly all SLE and ANCA-SVV patients express approximately 20% less CD19 than healthy control (HC) B cells. In contrast, a subset of memory B cells of some SLE and ANCA-SVV Pts (25-35%) express two to fourfold more CD19 than HC B cells. These CD19(hi) memory B cells are activated and exhibit evidence of antigen selection. Proteome array analysis of 67 autoantigens indicates that CD19(hi) SLE Pts exhibit a distinct autoantibody profile characterized by high levels of antibodies to small nuclear ribonucleoproteins and low levels of antiglomerular autoantibodies. These findings have implications for autoreactive B-cell activation and suggest a shared mechanism of B-cell tolerance loss in these two diseases.

   Keywords:
   Adult • Antibodies, Antineutrophil Cytoplasmic • Antigens, CD19 • Autoantibodies • Autoimmune Diseases* • B-Lymphocyte Subsets • B-Lymphocytes • Female • Flow Cytometry • Glomerulonephritis • Humans • Immune Tolerance • Lupus Erythematosus, Systemic • Lupus Nephritis • Lymphocyte Activation • Male • Middle Aged • Protein Array Analysis • Vasculitis • analysis • immunology • immunology* • methods